LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Distribution of pathogenic bacteria and antimicrobial sensitivity of eye infections in Suzhou.

AIM: To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs. METHODS: The clinical data of 155 patients were retrospectively collected in this study, and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed. RESULTS: Among the 155 patients (age from 12 to 87 years old, with an average age of 57, 99 males and 56 females) with eye infections (160 eyes: 74 in the left eye, 76 in the right eye and 5 in both eyes, all of which were exogenous), 71 (45.81%) strains were gram-positive bacteria, 23 (14.84%) strains were gram-negative bacteria and 61 (39.35%) strains were fungi. Gram-positive bacteria were highly resistant to penicillin and erythromycin (78.87% and 46.48% respectively), but least resistant to vancomycin at 0. Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole (100% and 95.65% respectively), but least resistant to meropenem at 0. Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences (P<0.05) in the resistance of both to cefoxitin, cotrimoxazole, levofloxacin, cefuroxime, ceftriaxone and ceftazidime, and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria. The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva, cornea, aqueous humor or vitreous body and other eye parts. Besides, Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections. CONCLUSION: Gram-positive bacteria are the dominant bacteria in eye infections, followed by gram-negative bacteria and fungi. Considering the resistance of gram-negative bacteria to multiple drugs, monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.

Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

Proteomic analysis of serum extracellular vesicles from biliary tract infection patients to identify novel biomarkers.

Biliary tract infection (BTI), a commonly occurring abdominal disease, despite being extensively studied for its initiation and underlying mechanisms, continues to pose a challenge in the quest for identifying specific diagnostic biomarkers. Extracellular vesicles (EVs), which emanate from diverse cell types, serve as minute biological entities that mirror unique physiological or pathological conditions. Despite their potential, there has been a relatively restricted exploration of EV-oriented methodologies for diagnosing BTI. To uncover potent protein biomarkers for BTI patients, we applied a label-free quantitative proteomic method known for its unbiased and high-throughput nature. Furthermore, 192 differentially expressed proteins surfaced within EVs isolated from individuals afflicted with BTI. Subsequent GO and KEGG analyses pinpointed Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and Crumbs homolog 3 (CRB3) as noteworthy biomarkers. Validation via data analysis of plasma-derived EV samples confirmed their specificity to BTI. Our study leveraged an unbiased proteomic tool to unveil CEACAM1 and CRB3 as promising protein biomarkers in serum EVs, presenting potential avenues for the advancement of diagnostic systems for BTI detection.

A novel modified polydopamine based on melanin-like materials for antibacterial, hydrophobic, and ultraviolet protective of textiles.

The development of environmentally friendly multifunctional auxiliaries for textile modification is the focus of attention in textile industry in recent years. Polydopamine is an important biological macromolecule and widely used in biomedicine, nanomaterials, material surface modification and other fields. In this study, the novel multifunctional melanin-like nanoparticles (Nha-PDA NPs) were prepared and used for antibacterial, hydrophobic, and UV protective of textiles. Nha-PDA NPs were prepared with dopamine (DA) and n-hexylamine (Nha) by simple autoxidation copolymerization. Nha-PDA NPs were bound to the fabric surface through the PDA structure in Nha-PDA NPs that has been widely confirmed to have strong adhesion on the surface of many materials. The modified fabrics, Nha-PDA NPs@Cotton, had good hydrophobic, antibacterial and UV protective properties. The static water contact angles of the modified fabrics could reach 120°. The antibacterial rates of Nha-PDA NPs@Cotton against E. coli and S. aureus were above 85 %. The maximum UPF value of the modified cotton was 362, indicating that the ultraviolet protection performance was excellent. The fabric modified with multifunctional melanin-like nanoparticle provides a green way for the multifunctional modification of textiles.

Phenotype of Takayasu-like vasculitis and cardiopathy in patients with Blau syndrome.

OBJECTIVES: We aimed to determine the prevalence of cardiovascular involvement in our Blau syndrome (BS) cohort and provide detailed analysis of their cardiovascular manifestations and outcome. We also tried to find out the risk factors for developing cardiovascular involvement. METHODS: Clinical manifestations, laboratory findings, and treatments were reviewed. Clinical features were compared between children with cardiovascular involvement and those without angiocardiopathy. RESULTS: A total of 38 BS children were eligible for final analysis. Among them, 13 (34.2%) developed Takayasu-like vasculitis and/or cardiopathy. Compared with those without angiocardiopathy, recurrent fever was more frequent in BS patients with cardiovascular involvement (p < 0.001). What is more, tumor necrosis factor alpha antagonists (anti-TNF) were more urgently needed in children with cardiovascular involvement (p = 0.015). BS patients with cardiovascular involvement include 4 with Takayasu-like vasculitis and 9 with cardiopathy. The onset of cardiovascular manifestations ranged from 0.75 to 18.5 years of age, with most cases occurring before school period. Symptoms were elusive and lacked specificity, such as dizziness, short of breath, and edema. Some patients were even identified because of the unexpected hypertension during follow-up. Cardiopathy and vasculitis occurred in patients with different genotypes. Imaging changes were discovered before the presentation of the typical triad in 3/4 patients with Takayasu-like vasculitis. Three children developed left ventricular dysfunction with decreased left ventricular ejection fraction. Combination of glucocorticoids and methotrexate with anti-TNF agents is a common treatment option for these BS patients. In the cohort, BS-related cardiovascular involvement was controlled well, with cardiac structural and functional abnormalities completely recovered and slower progression of vasculitis lesions. CONCLUSION: Cardiovascular manifestations is not rare in BS patients. Because of its insidious onset, a systematic and comprehensive assessment of cardiovascular involvement should be performed in newly diagnosed patients with BS. Aggressive initiation of anti-TNF agents may be beneficial to improve the prognosis. Key Points • About 34.2% patients with Blau syndrome developed Takayasu-like vasculitis and/or cardiopathy. • Compared with those without angiocardiopathy, recurrent fever and application of anti-TNF agents were more frequent in BS patients with cardiovascular involvement (p < 0.001, p = 0.015) • Regular assessment of cardiovascular involvement is extremely necessary because of its insidious onset.

A dominant pathogenic MEFV mutation causes atypical pyrin-associated periodic syndromes.

Pyrin, a protein encoded by the MEFV gene, plays a vital role in innate immunity by sensing modifications in Rho GTPase and assembling the pyrin inflammasome, which in turn activates downstream immune responses. We identified a novel and de novo MEFV p.E583A dominant variant in 3 patients from the same family; the variant was distinct from the previously reported S242 and E244 sites. These patients exhibited a phenotype that diverged from those resulting from classical MEFV gene mutations, characterized by the absence of recurrent fever but the presence of recurrent chest and abdominal pain. Colchicine effectively controlled the phenotype, and the mutation was found to induce pyrin inflammasome assembly and activation in patients' peripheral blood mononuclear cells (PBMCs) and cell lines. Mechanistically, truncation experiments revealed that the E583A variant affected the autoinhibitory structure of pyrin. Our study offers insights into the mechanisms underlying pyrin inflammasome activation.

Point-of-care ultrasound diagnosis of skull fracture in Chinese children 0-6 years old with scalp hematoma from minor head trauma: A preliminary prospective observational study.

Background: Previous studies have suggested that point-of-care ultrasound could help to evaluate and diagnose pediatric skull fracture for the closed scalp hematoma from blunt trauma. However, relevant data in Chinese children are missing, especially in children 0-6 years old. Objectives: Our study aimed to evaluate the efficacy of point-of-care ultrasound to diagnose skull fracture in children 0-6 years old with scalp hematoma in China. Methods: We performed a prospective observational study and screened children 0-6 years old with closed scalp hematoma and a Glasgow coma scale of 14-15 at Hospital in China. Enrolled children (N = 152) were first evaluated for skull fracture with point-of-care ultrasound by the emergency physician and then received a head computed tomography scan. Results: The point-of-care ultrasound examination and computed tomography scan revealed skull fracture in 13 (8.6%) and 12 (7.9%) children, respectively. The kappa test showed a satisfactory agreement between two examinations (P < 0.0001), with kappa = 0.87 (95% confidence interval, i.e., 95% CI, [0.69, 1.00]) and area under the curve = 0.95 (95% CI [0.86, 1], P < 0.0001). The point-of-care ultrasound examination had the sensitivity of 91.7% (95% CI [62.5%, 100%]), specificity of 98.6% (95% CI [94.6%, 100%]), positive predictive value of 84.6% (95% CI [56.5%, 96.9%]), negative predictive value of 99.2% (95% CI [95.6%, 100%]), and accuracy of 98.0% (95% CI [94.1%, 99.6%]). Conclusions: While our study is preliminary in nature, our findings may guide future larger studies in assessing the utility of point-of-care ultrasound examination in diagnosing skull fractures in children with scalp hematoma from minor head trauma.

Clinical phenotypes and prognosis of cytomegalovirus infection in the pediatric systemic lupus erythematosus: a longitudinal analysis.

BACKGROUND: Cytomegalovirus (CMV) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, it is not clear whether the anti-CMV treatment has an impact on the prognosis of SLE patients with CMV infection. We aimed to analyze the clinical characteristics and prognosis of CMV infection in pediatric SLE (pSLE) and to evaluate the effect of anti-CMV treatment on pSLE outcome. METHODS: A retrospective study including 146 pSLE from 2012 to 2021 was conducted. CMV-positive and CMV-negative groups were compared by univariate analysis and stepwise logistic multiple regression to analyze the clinical characteristics of CMV infection in pSLE. Generalized estimating equations (GEE) were used to model the longitudinal dynamics of pSLE disease activity with or without CMV infection and anti-CMV treatment. RESULTS: The CMV infection rate was 74.7% (109/146) in this pSLE cohort. CMV-positive pSLE patients were more likely to present positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement (P < 0.05). Survival analysis showed that CMV-positive pSLE patients were more prone to disease flare and poorer outcomes. GEE modeling indicated that CMV phosphoprotein 65 (pp65) titers were positively correlated with SLEDAI-2K, and anti-CMV treatment could better reduce pSLE activity than non-treatment (P < 0.05). CONCLUSIONS: CMV infection is highly prevalent among pSLE patients. Positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement were significant clinical clues indicating CMV infections in pSLE. CMV infection is correlated with higher disease activity and poorer outcome. Anti-CMV treatment can reduce disease activity and flares.

Boosting Activity and Selectivity of UiO-66 through Acidity/Alkalinity Functionalization in Dimethyl Carbonate Catalysis.

The acid-base properties of supports have an enormous impact on catalytic reactions to regulate the selectivity and activity of supported catalysts. Herein, a train of Pd-X-UiO-66 (X = NO2 , NH2 , and CH3 ) catalysts with different acidity/alkalinity functional groups and encapsulated Pd(II) species is first developed, whose activities in dimethyl carbonate (DMC) catalysis are then investigated in details. Thereinto, the Pd-NO2 -UiO-66 catalyst with acidity functionalization exhibits the best catalytic behavior: the DMC selectivity stemmed from methyl nitrite (MN) is up to 68%, the conversion of CO is 73.4%. The obtained experimental results demonstrate that the NO2 group not only affected the interaction between X-UiO-66 and Pd(II) active sites but also play an indispensable role in the adsorption and activation of MN and CO, which remarkably promote the formation of the COOCH3 * intermediate and DMC product.

Unique mutation spectrum of progressive pseudorheumatoid dysplasia in the Chinese population: a retrospective genotype-phenotype analysis of 105 patients.

BACKGROUND: Progressive pseudorheumatoid dysplasia (PPRD) is a rare genetic disease with autosomal recessive inheritance. There was a lack of genotype-phenotype correlation data from the Chinese population. This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD patients. METHODS: Genetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital. Medical records were collected from the electronic medical record system and patient-held portable health records. Published Chinese PPRD cases were gathered from both international and Chinese local databases. We collected demographic information, genetic variants, clinical manifestations, and imaging characteristics for further analysis. RESULTS: We included 105 Chinese PPRD patients in the current study. Thirty-three variants, including nine novels and five hotspot variants, were identified, with 26/33 (79%) variants exclusively seen in the Chinese population. Chinese PPRD patients share a phenotype similar to that in international reports. Joint involvement may progress with age (R2 = 0.2541). Long bone shortening and severe deformities occur in three patients with biallelic null variants, of which at least one variant is located in exon 2. Among hotspot variants, c.624dupA (p.C209Mfs*21) were associated with later onset and more involved joints. Elbow joints were more likely to be affected in patients carrying c.624dupA (p.C209Mfs*21) and c.866dupA (p.S209Efs*13). Shoulder joints are more likely to be involved in patients with biallelic null variants (P = 0.027). CONCLUSIONS: Chinese PPRD patients share a unique mutation spectrum. Among the five hotspot variants, c.624dupA is associated with later onset of disease, more extensive joint involvement, and a tendency to affect elbow joints. Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia: a propensity score matching analysis.

Objective: Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population. Methods: A retrospective analysis of the clinical data of 116 children with CDH was conducted. The children were assigned to EXIT and non-EXIT groups. Propensity score matching (PSM) toward clinical data was performed, and the clinical characteristics and outcomes were compared. Taking survival at discharge as the main outcome, logistic regression analysis was carried out to explore the efficacy of EXIT on survival. Results: During the study period, 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76% (24/29) and 48.28% (14/29), respectively (p=0.006). EXIT (OR=0.083, 95% CI=0.013to 0.525, p=0.008), liver herniation (OR=16.955, 95% CI=2.342 to 122.767, p=0.005), and gestational age at diagnosis (OR=0.662, 95% CI=0.497 to 0.881, p=0.005) were independent mortality-related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6% (22/26) and 76.9% (20/26), respectively (p=0.754). Liver herniation (OR=10.451, 95% CI=1.641 to 66.544, p=0.013) and gestational age at diagnosis (OR=0.736, 95% CI=0.577 to 0.938, p=0.013) were independent mortality-related risk factors of children after surgery. Conclusion: EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.

PSR-FCCLP model based total maximum allocated loads optimization of TN and TP in Bohai Bay.

Eutrophication is a global problem for coastal ecosystems, one that Bohai Bay, China, has been severely afflicted due to rapid economic and social development in the past decades. It was urgent to manage the total maximum allocated loads (TMALs) of the total nitrogen (TN) and total phosphorus (TP) on land-based, which was closely related to coastal eutrophication. In this study, from the perspective of economy-resources-environment (ERE) system, we presented the fuzzy credibility constrained linear programming based on pressure-state-response (PSR-FCCLP) model, which calculated the TMALs of TN and TP at three credibility levels (λ = 0.55, 0.75, and 0.95) in Bohai Bay. The results showed that when the credibility level increased from 0.55 to 0.95, the TMALs of TN and TP would decrease from 13,573.38 t/a to 12,820.00 t/a and from 2665.58 t/a to 2514.90 t/a, respectively. This study will provide support for environmental management in coastal regions.

Early indicators of neonatal-onset hereditary thrombotic thrombocytopenia purpura.

Background: Neonatal-onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO incompatibility. Objective: To explore early indicators of neonatal-onset hTTP. Methods: This study was a retrospective case series of newborns with hTTP and ABO incompatibility. We compared the clinical characteristics and laboratory test results in these two groups. Results: This study included four hTTP patients and 20 ABO-incompatible newborns. All patients manifested disease during the neonatal period. There were equal numbers of males and females in each group. hTTP newborns showed earlier (median difference, 57.0 h; 95% confidence interval [CI], 24.0-65.0) and more severe hyperbilirubinemia (mean difference, 8.0 mg/dl; 95% CI, 3.8-12.1) than ABO-incompatible newborns. In hTTP newborns, anemia was more common within 7 days after birth than in ABO-incompatible newborns (odds ratio, 25.4; 95% CI, 1.2-551.6), and platelet counts were lower than in ABO-incompatible newborns (17 ± 12 × 109/L vs. 291 ± 76 × 109/L). The levels of serum creatinine (median difference, 51.8 µmol/L; 95% CI, 16.0-109.4) and blood urea nitrogen (median difference, 5.7 mmol/L; 95% CI, 2.8-38.7) were higher in hTTP newborns than in ABO-incompatible newborns. There were no significant differences in white blood cell counts, C-reactive protein, alanine aminotransferase, or albumin levels. Conclusions: Severe jaundice soon after birth, early anemia, and severe thrombocytopenia were more common in newborns with hTTP than ABO incompatibility. These are distinguishing early features of hTTP.

Prognostic Significance of CCDC137 Expression and Its Association with Immune Infiltration in Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortalities. The clinical outcome of HCC patients remains poor due to distant metastasis and recurrence. In recent years, growing evidences have confirmed that the coiled-coil domain-containing (CCDC) family proteins are involved in the progression of several diseases. However, the expression and clinical significance of the coiled-coil domain-containing 137 (CCDC137) in hepatocellular carcinoma (HCC) have not been investigated. Level 3 mRNA expression profiles and clinicopathological data were obtained in TCGA-LIHC. Differentially expressed genes (DEGs) were screened between 371 HCC and 50 nontumor specimens. The prognostic value of CCDC137 was analyzed in HCC patients. The correlations between CCDC137 and cancer immune infiltrates were investigated. In this study, a total of 2897 DEGs were obtained: 2451 genes were significantly upregulated and 446 genes were significantly downregulated. KEGG assays revealed that these DEGs were involved in tumor progression. Among 2897 DEGs, we found that CCDC137 expression was distinctly increased in HCC specimens compared with nontumor specimens. A high level of CCDC137 expression was related to an advanced tumor stage and grade. Moreover, patients with higher levels of CCDC137 expression had a shorter overall survival and disease-free survival than patients with lower CCDC137 levels. CCDC137 expression was positively correlated with infiltrating levels of several immune cells, such as CD8 T cells and Th2 cells. Finally, in vitro experiments confirmed that CCDC137 expression was highly expressed in HCC cells, and its knockdown suppressed the proliferation of HCC cells. Taken together, our findings revealed that CCDC137 might be used as a biomarker for immune infiltration and poor prognosis in HCC, which offered fresh insight on potential therapies for HCC.

Electrochemical Oxidative C(sp2)-H Amination of Aldehyde Hydrazones with Azoles.

A general and highly efficient method for the electrochemical C(sp2)-H amination of aldehyde hydrazones with azoles has been developed. This reaction proceeds under exogenous metal-, catalyst-, and oxidant-free conditions to provide aminated hydrazone derivatives in good to excellent yields. This strategy applies to both aromatic and aliphatic aldehyde hydrazones and tolerates a broad range of functional groups.

Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study.

PURPOSE: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group). RESULTS: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group (75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P < 0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P = 0.037). CONCLUSIONS: CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.

Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China.

Objective: This study aimed to assess the efficacy and safety of 2 Janus kinase (JAK) inhibitors (jakinibs) tofacitinib and ruxolitinib in the treatment of type I interferonopathies patients including STING-associated vasculopathy with onset in infancy (SAVI), Aicardi-Goutières syndrome (AGS), and spondyloenchondrodysplasia with immune dysregulation (SPENCD). Methods: A total of 6 patients were considered in this study: 2 patients with SAVI, 1 patient with AGS1, 1 patient with AGS7, and 2 patients with SPENCD. Clinical manifestations, laboratory investigations, radiology examinations, treatment, and outcomes were collected between November 2017 and November 2021 in Peking Union Medical College Hospital. The disease score for patients with SAVI and AGS scale for patients with AGS were documented. The expression of 6 interferon-stimulated genes (ISGs) was assessed by real-time PCR. Results: Three patients (1 patient with SAVI, 2 patients with AGS) were treated with ruxolitinib and 3 patients (1 patient with SAVI, 2 patients with SPENCD) were treated with tofacitinib. The mean duration of the treatment was 2.5 years (1.25-4 years). Upon treatment, cutaneous lesions and febrile attacks subsided in all affected patients. Two patients discontinued the corticoid treatment. Two patients with SAVI showed an improvement in the disease scores (p < 0.05). The erythrocyte sedimentation rate normalized in 2 patients with AGS. The interferon score (IS) was remarkably decreased in 2 patients with SPENCD (p < 0.01). Catch-ups with growth and weight gain were observed in 3 and 2 patients, respectively. Lung lesions improved in 1 patient with SAVI and remained stable in 3 patients. Lymphopenia was found in 3 patients during the treatment without severe infections. Conclusion: The JAK inhibitors baricitinib and tofacitinib are promising therapeutic agents for patients with SAVI, AGS, and SPENCD, especially for the improvement of cutaneous lesions and febrile attacks. However, further cohort studies are needed to assess the efficacy and safety.

Overexpression of SLC25A51 promotes hepatocellular carcinoma progression by driving aerobic glycolysis through activation of SIRT5.

Solute carrier family 25 member 20 (SLC25A51) is a newly identified mammalian mitochondrial NAD+ transporter. However, the clinicopathological and biological significance of SLC25A51 in human cancers, including hepatocellular carcinoma (HCC), remains unclear. The aim of this study was to define the role of SLC25A51 in HCC progression. Here we demonstrate that SLC25A51 is significantly overexpressed in human HCC specimens and cell lines, caused by, at least in partial, the decrease of miR-212-3p. SLC25A51 overexpression is positively correlated with the clinicopathological characteristics of vascular invasion and tumor diameter, as well as poor survival in patients with HCC. Knockdown of SLC25A51 attenuated, while overexpression of SLC25A51 enhanced the growth and metastasis of HCC cells both in vitro and in vivo. Mechanistically, glucose metabolism reprogramming from oxidative phosphorylation to glycolysis by activation of mitochondrial sirtuin 5 (SIRT5) was found to contribute to the promotion of growth and metastasis by SLC25A51 in HCC cells. Together, these findings reveal important roles of SLC25A51 in HCC tumorigenesis and suggest SLC25A51 as a promising prognostic marker and therapeutic target for treating HCC.

Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. Exploring the correlation between the phenotype and genotype of NPHP-RC is helpful for early diagnosis and management. We investigated the phenotype and genotype spectra of NPHP-RC in a Chinese multicentre cohort. METHODS: Crosss-ectional and longitudinal data of 60 patients from 57 families with pathogenic NPHP-RC gene mutations distributed in 22 regions of China were collected into a unified, anonymous database. The mean observation time of this cohort was 3.5±3.1 years. RESULTS: Mutations in NPHP1 and NPHP3 were the most common genetic defects. Overall, 45% of patients presented with isolated nephronophthisis (NPH), and 55% exhibited the extrarenal phenotype, which frequently involved the liver (41.7%, n=25), central nervous system (26.7%, n=16), eyes (26.7%, n=16) and skeletal system (11.7%, n=7). Accidental detection of elevated serum creatinine and non-specific symptoms caused by chronic kidney disease occurred in 65% of patients. Patients carrying NPHP1 mutations mainly presented with isolated NPH (90%, 18/20) and progressed to ESRD at a mean age of 12.9±0.5 years. The mean age of ESRD onset in the non-NPHP1 group was lower than that in the NPHP1 group (6.2±1.4 years, p<0.001), especially for patients carrying NPHP3 mutations (3.1±1.2 years), showing a heterogeneous phenotype characterised by Bardet-Biedl syndrome (12.5%, n=5), Joubert syndrome (7.5%, n=3), COACH syndrome (2.5%, n=1), Mainzer-Saldino syndrome (2.5%, n=1), short-rib thoracic dysplasia (2.5%, n=1) and unclassified symptoms (32.5%, n=13). CONCLUSIONS: The Chinese Children Genetic Kidney Disease Database registry characterised the spectrum of the phenotype and genotype of NPHP-RC in the Chinese population. NPHP1 and NPHP3 were the most common pathogenic genes. Rapid progression to ESRD and liver involvement were noted in patients with NPHP3 mutations.